Iron is the most abundant transition metal species in the human body and is involved in various life phenomena, including oxygen transport and electron transfer in the respiratory system. However, abnormal levels of iron in the body have been suggested as being associated with serious diseases, such as cancer, Alzheimer's disease, and Parkinson's disease. In particular, Fe(II) ions, representing the large part of in vivo free iron ions, have been suspected of contributing to asbestos cancer or hepatitis C because of their high potential for generating reactive oxygen species (e.g., Patent Literature 1 and 2, and Non-patent Literature 1 to 5). A fluorescence probe capable of selectively detecting Fe(II) ions in living cells or living tissues, and at the same time acutely detecting a change in the concentration, when such a probe is developed, will be a tremendously important technique, for example, in research of diseases and life phenomena associated with Fe(II) ions, as well as pharmaceutical development.
Recent years have seen active development of fluorescence probes for labeling biomolecules, ions, and the like. For example, many fluorescence probes that have a fluorophore as a frame structure, such as fluorescein and rhodamine, have been reported (e.g., Patent Literature 3 and 4 and Non-patent Literature 6 and 7).
Fluorescence probes for detecting iron ions reported so far include a quenched iron ion detecting probe (e.g., Non-patent Literature 8 and 9). However, due to its low detection sensitivity or selectivity to iron ions, it is difficult to acutely detect a change in the concentration by using this probe.
Patent Literature 5 reports a fluorescence probe for measuring aluminium ions and/or ferric ion ions. However, the target of the probe is Fe(III) ions, not Fe(II) ions. Moreover, the selectivity of metal ions is unsatisfactory with this probe.
To solve the problems, Patent Literature 6 reports an Fe(II) ion detection fluorescence probe that has an N-oxide moiety (e.g., RhoNox-1; see FIG. 1). This fluorescence probe exploits the following characteristics; i.e., the N-oxide moiety reacts with an Fe(II) ion to thereby undergo deoxygenation, thus increasing fluorescence. Such a fluorescence probe producing a fluorescence-emission response to Fe(II) ions is very creative, making a clear departure from traditional fluorescence probes that produce a quenched response. The fluorescence probe is also excellent in detection sensitivity and selectivity to Fe(II) ions.
Non-patent Literature 10 to 12 report fluorescence probes that are improved versions of the fluorescence probe disclosed in Patent Literature 6 (e.g., RhoNox-1). Specifically, the fluorescence probes of Patent Literature 10 to 12 are compounds obtained by replacing the carboxyl in the rhodamine frame structure of RhoNox-1 with hydroxyl (e.g., HMRhoNox-M and HMRhoNox-E in FIG. 1).